Abnormal Facies Research Articles

Clinical and histopathological findings in Bannayan-Riley-Ruvalcaba syndrome

Bannayan-Riley-Ruvalcaba syndrome is a rare autosomal dominant genodermatosis with the classical triad of macrocephaly, genital lentiginosis, and intestinal polyposis. Characteristic mucocutaneous manifestations include vascular malformations, lipomatosis, speckled lentiginosis of the penis or vulva, facial verrucae-like or acanthosis nigricans-like lesions, and multiple acrochordons of the neck, axilla, and groin. We present a case of Bannayan-Riley-Ruvalcaba syndrome with macrocephaly, abnormal facies, lipoma, tender and painful arteriovenous hemangiomas, lymphangiokeratomas, musculoskeletal abnormalities, and localized myopathy. We also describe previously unreported findings, including peripheral neuropathy, punctate cystic changes in acral tubular bones, and enostosis of talus. Bannayan-Riley-Ruvalcaba syndrome needs recognition by dermatologists because affected patients may present with mucocutaneous and subcutaneous lesions that may simulate other dermatological disorders.

Chromosome 22q11 Deletions in Patients with Conotruncal Heart Defects

We performed this study to determine the frequency of 22q11 deletions and associated phenotypic features and abnormalities in conotruncal heart defects. Sixty-one patients with conotruncal heart defects, including tetralogy of Fallot (TOF; n = 32), pulmonary atresia/ventricular septal defect (PAVSD; n = 12), double-outlet right ventricle (DORV; n = 5), transposition of the great arteries (TGA; n = 4 ), truncus arteriosus (TA; n = 4), subpulmonary ventricular septal defect (SPVSD; n = 3), and interrupted aortic arch (IAA; n = 1), were enrolled in this study and screened for 22q11 deletions by the fluorescence in situ hybridization technique. Phenotypic features and associated abnormalities, including submucosal cleft palate, abnormal facies, square nose, nasal voice, abnormal ears, long and slender fingers, delayed development, mental retardation, delayed growth, short stature, and hypocalcemia, were examined in these patients. Nine of 61 patients (14.8%) had 22q11 deletions, including 100% of IAA, 50% of TA, 33.3% of SPVSD, 33.3% of PAVSD, and 3.1% of TOF. Deletions were not detected in DORV and TGA. In all patients with 22q11 deletions, > or =1 phenotypic features or associated abnormalities were observed. A subgroup of patients with IAA, TA, SPVSD, and PAVSD associated with phenotypic features or abnormalities warrants evaluation for the presence of 22q11 deletions.

The Distal Arthrogryposes

Distal arthrogryposes are a group of syndromes with congenital contractures primarily involving the hands and feet, which often are associated with abnormal facies, and are transmitted by autosomal dominant inheritance. Many affected individuals present in an orthopaedic setting. The features of these syndromes are described to allow diagnosis, establish prognosis, provide family counseling, and treatment. Increased recognition will lead to improved knowledge of the natural history.

T cell depletion in Wolf-Hirschhorn syndrome

Rationale Wolf-Hirschhorn syndrome (WHS), a genetic disorder due to a partial deletion of chromosome 4p16.3 has characteristic features such as, facial abnormalities (i.e. microcephaly and frontal bossing), cardiac malformations, and mental retardation. B cell defects have also been described in several patients with WHS. However, T cell immunity has been noted to be normal in all previous reported subjects. We present a unique case of a child with WHS associated with a cell-mediated immunodeficiency. Case report Genetic analysis of a 6 month old male with abnormal facies, an atrial septal defect, and failure to thrive revealed a microdeletion in 4p16.3 position consistent with WHS. The patient presented with recurrent skin abscess at 2 1/2 years of age. Culture of the abdominal abscess grew methicillin resistant S. aureus. Methods and results Immunological evaluation revealed the following: Normal CBC; NBT 100%; Chemiluminescence assay, 32.6 × 10 6 CMP; total hemolytic complement, 70. Lymphocyte subset enumeration revealed an absolute CD4 count of 473. Lymphocyte proliferation assay revealed low responses following tetanus, S. aureus and Candida stimulations. However, evaluation of humoral immune function was found to be normal; antibody responses to diphtheria, tetanus and pneumococcal vaccines were in normal range. FISH analysis of chromosome 22q11 was found to be normal. The abdominal abscess responded to Clindamycin and Rifampin. Conclusions Cell-mediated immunodeficiency can be seen in patients with WHS in the absence of humoral defects. WHS patient who have recurrent or persistent infections should have a complete immune evaluation, including cell-mediated immunity.

Chronostratigraphy of proposed Turonian-Coniacian (Upper Cretaceous) stage boundary stratotypes: Salzgitter-Salder, Germany, and Wagon Mound, New Mexico, USA

Abstract A knowledgeable choice for a stage boundary stratotype is dependent upon obtaining high-resolution stratigraphic data. Detailed analyses conducted for the two potential Turonian-Coniacian stage boundary stratotypes that were considered at the Second Cretaceous Stage Boundary Symposium provide both positive and negative insights for consideration. The Salzgitter-Salder Quarry in central Germany (which was recommended by the symposium) contains abundant bivalve fossils, including the recommended boundary datum: the lowest occurrence of the inoceramid bivalve Cremnoceramus deformis erectus . Foraminifera are also abundant, but extensive diagenetic recrystallization seriously degrades nannofossil and palynomorph recovery and limits the potential of the section for stable isotope stratigraphy and radiometric dating. Furthermore, palaeoenvironmental analysis indicates that much of the Salzgitter stage boundary interval has resulted from allochthonous sedimentation, indicating that the well-developed lithological cyclicity between limestone and marlstone that occurs in the section is largely autocyclic. The orbital cyclostratigraphic potential of the section is therefore also in question. The Wagon Mound outcrop in northeastern New Mexico, USA, has good recovery and biostratigraphic control for all three microfossil groups, but the base of C. deformis erectus occurs above the section, by definition placing the section entirely in the Upper Turonian Well-preserved ammonites and inoceramid bivalves are also recoverable in over half of this section. Facies have not been recrystallized and represent continuous autochthonous sedimentation with sharply defined lithological cyclicity between limestone/marlstone couplets on a fine stratigraphic scale. In addition, a number of bentonites with proven datability occur in the section. Thus the bio- and chemostratigraphic dating potential, as well as the radiometric dating potential, of the section are good. However, much of the section is composed of carbonaceous, dysoxic facies with abnormal marine micro- and macrofossil assemblages, limiting study of the stratigraphic or palaeoecological trends leading up to the boundary. The absence of the datum at Wagon Mound is puzzling, because microfossil biostratigraphy suggests that the section is substantially coeval with the Salzgitter-Salder section. The C. deformis erectus datum may thus be diachronous. Until the suitability of the recommended boundary datum is addressed, a reasoned choice of a section for the boundary stratotype is not possible. In any case, the absence of C. deformis erectus and the abnormal facies in the lower part of the Wagon Mound section, and the extensive diagenesis and partly allochthonous nature of the Salzgitter-Salder section, are serious enough problems to warrant rejection of both sections as stratotypes.

Interstitial deletion of 13q and a 13;X chromosome translocation results in partial trisomy 13 and bilateral retinoblastoma

Background: Abnormalities of chromosome 13 have been associated with bilateral retinoblastoma. Deletion of a retinoblastoma gene is a common primary mechanism. Other abnormalities are more rare. To our knowledge, a balanced translocation of the long arms of the X and 13 chromosomes associated with bilateral retinoblastoma has been reported five times. We report an unbalanced X;13 translocation resulting in partial trisomy 13 and an interstitial deletion of an RB locus. Methods: Case report. Results: A 19-month-old child presented with seizures to the emergency department. A CT scan revealed bilateral intraocular calcification, and retinoblastoma (RB) was confirmed with an ophthalmic exam. Abnormal facies and developmental delay were noted. A partial trisomy derived from the translocation of X;13 was observed in both bone marrow and peripheral blood cells. Fluorescence in-situ hybridization (FISH) studies confirmed triplication of a region on the q arm of chromosome 13 spanning the RB locus. One of the normal chromosome 13 homologues had an interstitial deletion of the RB locus since no signal was observed for the RB-1 probe despite the visible presence of the 13q14 region. Additional evidence of the interstitial deletion is supported by the typical facial features and developmental delay found. Presumably, the translocated X underwent X inactivation precluding systemic features typically observed in trisomy 13. Parental karyotypes were normal. The chromosomal abnormality was a de-novo constitutional event. Conclusions: Only two RB loci were present in this patient despite triplication of 13q. The third locus was deleted. We believe that the second locus was not expressed due to X inactivation of the RB gene on the der(X)t(Xq:13q) chromosome. The emergence of bilateral retinoblastoma points towards lack of heterozygosity at the third and last remaining RB loci in tumor cells. To our knowledge, an unbalanced translocation resulting in partial trisomy 13 with retinoblastoma has not been previously reported.

P72Prenatal assessment of the thymus in detecting fetuses with del.22q

BackgroundSome congenital heart defects (CHD) were found to be associated with a deletion 22q11 and grouped as catch‐22 an acronym for Cardiac anomaly, Abnormal facies, Thymus hypo‐ or aplasia, Cleft palate and Hypothyreoidism with del.22q.11. It is still discussed whether all fetal CHD or only conotruncal anomalies (CTA) should get the targeted del.22q11 evaluation. Aim of the study was to find out the importance of thymus visualization in the prenatal detection of these affected fetuses.MethodDuring a period of 3 years only fetuses with CHD undergoing invasive procedure for determination of the karyotype and fish for del.22q11 were included in the study. Fetal thymus was visualized as the structure in front of the great vessels as seen in the three‐vessels‐trachea view.Results95 fetuses with different CHD were evaluated including 31 with conotruncal anomalies. Seven fetuses were found to have a del.22q11 (7.3% of all CHD, 22.5% of CTA). Six of these 7 (85.7%) had no or a hypoplastic thymus. A false positive result was found in two further cases.ConclusionsFetal thymus can be assessed on prenatal ultrasound. In fetuses with CHD especially in CTA the absence or hypoplasia of the thymus can be a hint in the targeted examination for del.22q11.

The extreme Spectrum of Pallister-Hall syndrome

Pallister-Hall syndrome can result from GLI 3 gene mutation and is characterized by hypothalamic hamartoblastoma, hypopituitarism, imperforate anus, and postaxial polydactyly. It has a wide spectrum of severity, from perinatal lethal to minimally symptomatic. Familial cases with different expressiveness were reported before. We herein report a 22-week terminated fetus, which was a product of a GIPO 16-year-old healthy mother. Initial ultrasound at 20 weeks gestation revealed severe oligohydramnios and a small fetus. Subsequent ultrasound revealed absent stomach, dysplastic kidneys, short limbs, distal dysplasia, abnormal facies and the possibility of Roberts syndrome was discussed. The patient was counseled and pregnancy termination was sought. Cytogenetic studies revealed a normal 46,XY male karyotype and negative study for centromere analysis. Autopsy revealed a normally grown 22-23 week male fetus with hypothalamic hamartoma, polydactyly, imperforate anus and multiple other congenital anomalies. He had small, wide-spaced eyes, bilateral choanal atresia, soft tissue mass of the philtrum, small mouth with soft tissue fusion between alveolar ridges, lips and tongue, abnormal palate with possible midline clefting, micrognathia and simple lowset ears. There were short upper extremity digits with hypoplastic nail bed and bilateral partial duplication and fusion of the fourth digits. The feel were markedly everted with small medially placed great toes. The third, fourth and fifth digits are all short with poor nail bed. All digits had prominent syndactyly. There was anal atresia with blind rectosigmoid colon emptying into the bladder region without rectovesicular fistula. There was bilateral renal hypoplastic dysplasia with disorganization of the cortex. Brain examination revealed hypothalamic hamartoblastoma, 1.0 × 1.5 × 1.0 cm. There was absent cerebellar vermis, absent corpus callosum, probable absent olfactory grooves and tracts and sella turica wilh no pituitary gland present. Small adrenal glands with disorganization of the adrenal cortex were also noted. Cardiac exam revealed malrotation of the great vessels and cardiomegaly. Pulmonary hypoplasia and oligohydramnios sequence was noted with flexion conlractures of the joints. Our patient represents an extreme spectrum of PHS and emphasizes the importance of recognition of fetal syndrome and documented autopsy for genetic counseling.

Larsen’s syndrome

A 1-day-old female full-term newborn had mild-to-moderate episodic inspiratory stridor. She had no retractions or cyanosis, her cry and feeding were normal, and the stridorous episodes typically occurred while she was crying. Genetic and orthopedic consultations were obtained for abnormal facies and knee and hip dislocations.

慢性中耳炎を伴ったＣＡＴＣＨ２２症候群例

CATCH22 syndrome, as defined by D. I. Wilson, is associated with the following features: Cardiac anomalies, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcemia resulting from microdeletions of chromosome 22q11. We encountered a patient with chronic otitis media, who was diagnosed as having CATCH22. We performed a right tympanoplasty and reported subsequent findings in this CATCH22 patient.The case was a 9-year-old female who complained of bilateral otorrhea. She was diagnosed with CATCH22 syndrome on the basis of clinical findings and a genetic analysis before visiting our clinic. Tympanoplasty revealed the handle of the malleus to be severely bent and ossicular movements seemed to be slightly restricted. Other anomalies were not observed. She was discharged without any further symptoms.

Sotos syndrome and cutis laxa

Characteristics suggestive of connective tissue dysfunction have been described in Sotos syndrome and include joint hyperextensibility, pes planus, and a high arched palate. A variety of cutis laxa syndromes have...

A signaling cascade involving endothelin-1, dHAND and msx1 regulates development of neural-crest-derived branchial arch mesenchyme.

Numerous human syndromes are the result of abnormal cranial neural crest development. One group of such defects, referred to as CATCH-22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia, associated with chromosome 22 microdeletion) syndrome, exhibit craniofacial and cardiac defects resulting from abnormal development of the third and fourth neural crest-derived branchial arches and branchial arch arteries. Mice harboring a null mutation of the endothelin-1 gene (Edn1), which is expressed in the epithelial layer of the branchial arches and encodes for the endothelin-1 (ET-1) signaling peptide, have a phenotype similar to CATCH-22 syndrome with aortic arch defects and craniofacial abnormalities. Here we show that the basic helix-loop-helix transcription factor, dHAND, is expressed in the mesenchyme underlying the branchial arch epithelium. Further, dHAND and the related gene, eHAND, are downregulated in the branchial and aortic arches of Edn1-null embryos. In mice homozygous null for the dHAND gene, the first and second arches are hypoplastic secondary to programmed cell death and the third and fourth arches fail to form. Molecular analysis revealed that most markers of the neural-crest-derived components of the branchial arch are expressed in dHAND-null embryos, suggesting normal migration of neural crest cells. However, expression of the homeobox gene, Msx1, was undetectable in the mesenchyme of dHAND-null branchial arches but unaffected in the limb bud, consistent with the separable regulatory elements of Msx1 previously described. Together, these data suggest a model in which epithelial secretion of ET-1 stimulates mesenchymal expression of dHAND, which regulates Msx1 expression in the growing, distal branchial arch. Complete disruption of this molecular pathway results in growth failure of the branchial arches from apoptosis, while partial disruption leads to defects of branchial arch derivatives, similar to those seen in CATCH-22 syndrome.

Delineating a 22q11 deletion subtype of schizophrenia

Congenital heart diseases (CHDs) are the most common of all birth defects. Congenital heart disease may occur as an isolated malformation or may be part of a syndrome. One of the most common syndromes associated with CHDs is the 22q11.2 microdeletion syndrome, the various conditions associated with del22q11 include DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), conotruncal anomaly face syndrome (CTAFS), and others. The abnormalities associated with this syndrome include parathyroid hypoplasia, thymic hypoplasia, immune defect, cleft palate, and abnormal facies. The cardiac defects are usually derived from conotruncus.The aim of the study was to detect the prevalence and the most common or frequent clinical manifestations of chromosome 22q11.2 microdeletion among children with syndromic congenital heart disease.The study was conducted on 20 children with syndromic CHD presenting to the Menoufiya University Hospitals, Egypt. Their ages ranged from 10 days to 12 years. Cytogenetic study and fluorescence in situ hybridization (FISH) were performed in the patients. The study revealed that 2 patients were with chromosomal aberrations [one with 46,XY, add (13)(p13) & the other with 47,XX,+13]. In addition, FISH revealed 4 patients (20%) with 22q11.2 microdeletion syndrome. The congenital heart malformations detected in patients with 22q11.2 microdeletion were somewhat unexpected and included VSD, ASD, PDA, and double outlet right ventricle. The most frequent extracardiac features were hypocalcemia, microcephaly, brain atrophy, epicanthus, low set posteriorly rotated ears, micrognathia, and anemia. The extracardiac features were in some cases subtle.It is concluded that 22q11.2 microdeletion is not uncommon and its manifestations are highly variable. This entails that screening for the microdeletion by FISH should be performed in all patients with syndromic CHD especially those with hypocalcemia, microcephaly, brain atrophy, epicanthus, low set ears, posteriorly rotated ears, micrognathia, and anemia. In addition, patients with minor features and those with non-conotruncal heart disease should not be excluded from the screening for 22 microdeletion.

The Molecular Basis of Congenital Cardiac Disease

Today, congenital cardiovascular disease is virtually always amenable to corrective or palliative surgical interventions. However, the mechanisms causing developmental anomalies of the heart and vessels have remained obscure until recently. This review presents genetic defects causing the pediatric vasculopathies; Marfan's syndrome, inherited supravalvar aortic stenosis, and Williams' syndrome. A synopsis of known mutations causing human cardiomyopathies in nuclear genes encoding contractile proteins, cardiomyocyte structural proteins, and mitochondrial proteins essential for cardiac energy production is provided. The molecular genetic evidence implicating single gene mutations in the pathogenesis of conotruncal anomalies (the 22q11 monosomy or "cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, and hypocalcemia with deletions on chromosome 22" [CATCH-22] syndrome), heterotaxy syndromes, trisomies and atrioventricular canal defects, and secundum atrial septal defects is presented. The consequences of these genetic causes for diagnostic evaluation and perioperative care are emphasized. Single gene defects are a common cause of congenital cardiac disease. Copyright 1998 by W.B. Saunders Company

Microdeletion 22q11 in complex cardiovascular malformations.

Besides DiGeorge, velocardiofacial and conotruncal anomaly face syndromes, some of the isolated congenital heart diseases have also been associated with a chromosomal deletion in 22q11. These disease entities, which had originally been considered to have a different genetic background, are now included in the CATCH-22 microdeletion complex. CATCH 22 is an acronym for cardiac defect, abnormal facies, thymic hypoplasia or aplasia and T-cell deficiency, cleft palate, hypoparathyroidism, and hypocalcemia. In the present study, we focused on the complex cardiovascular defects (CCVD) and screened 40 patients for a microdeletion of 22q11 by fluorescence in situ hybridization using the D22S75 DNA probe and for associated CATCH features. The patients were from genetic counseling (n = 15) or fetopathology (n = 3) of the Clinical Genetics Department in Marburg and from the Pediatric Cardiology Department (n = 22) in Mainz. Monosomy 22q11 was detected in 9 cases (= 22.5%). Familial transmission with one mildly affected parent and one affected sib each was proven in two cases. The CCVDs comprised complex conotruncal defects such as tetralogy of Fallot, double outlet right ventricle, transposition of great arteries and truncus arteriosus communis, or anomalies of the derivatives of the branchial arch arteries in association with a ventricular septal defect, including one case of atresia of the ductus arteriosus with pulmonary artery aneurysm and resulting in fetal hydrops. All 13 patients with a deletion of 22q11 showed at least one additional CATCH symptom. Most consistently, facial dysmorphy was apparent (92%), while hypocalcemia, mostly at threshold values, was present in 62% and thymic hypoplasia including borderline low T-lymphocyte numbers was observed in 41%. None of the patients presented with a cleft palate. A high intrafamilial variability in expression was also evident with respect to the CCVD. Our findings indicate that seemingly isolated complex cardiovascular defects associated with a 22q11 microdeletion most probably do not represent a distinct subgroup within the CATCH-22 complex but are syndromal in nature with extracardiac features that are often overlooked.

UFD1L, a developmentally expressed ubiquitination gene, is deleted in CATCH 22 syndrome.

The CATCH 22 acronym outlines the main clinical features of 22q11.2 deletions (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate and hypocalcemia), usually found in DiGeorge (DGS) and velo-cardio-facial (VCFS) syndromes. Hemizygosity of this region may also be the cause of over 100 different clinical signs. The CATCH 22 locus maps within a 1.5 Mb region, which encompasses several genes. However, no single defect in 22q11.2 hemizygous patients can be ascribed to any gene so far isolated from the critical region of deletion. We have identified a gene in the CATCH 22 critical region, whose functional features and tissue-specific expression suggest a distinct role in embryogenesis. This gene, UFD1L, encodes the human homolog of the yeast ubiquitin fusion degradation 1 protein (UFD1p), involved in the degradation of ubiquitin fusion proteins. Cloning and characterization of the murine homolog (Ufd1l) showed it to be expressed during embryogenesis in the eyes and in the linear ear primordia. These data suggest that the proteolytic pathway that recognizes ubiquitin fusion proteins for degradation is conserved in vertebrates and that the UFD1L gene hemizygosity is the cause of some of the CATCH 22-associated developmental defects.

Moebius syndrome: a review of the anaesthetic implications.

Moebius syndrome is a rare congenital anomaly characterized by multiple cranial nerve palsies, orofacial malformations and limb anomalies. This study retrospectively reviewed the anaesthetic records of 19 children with Moebius syndrome who had anaesthesia at the Royal Alexandra Hospital for Children over a 15 year period and analysed the complications which occurred. Affected children most commonly present for anaesthesia for correction of strabismus, or for orthopaedic procedures to improve limb function. Despite the abnormal facies and drooling of saliva, these children are almost always of normal intelligence. Problems can arise during anaesthesia, with a high incidence of difficult or failed intubation. The use of a facemask and spontaneous breathing technique, where appropriate, seems to present no problems and maintaining an airway in this way appears to be safe. However, the potential for problems with aspiration of oral secretions should be remembered and the use of antisialogogue premedication is recommended. Affected children have a high incidence of other anomalies, including congenital cardiac disease, spinal anomalies, corneal abrasions and peripheral neuropathies and a careful preoperative assessment is essential.

DNA Fluorescent Probes for Diagnosis of Velocardiofacial and Related Syndromes

To study the usefulness of fluorescent in situ hybridization (FISH) with the DNA probe D22S75 for detecting microdeletions in chromosome 22q11.2 in metaphases from patients with features of "CATCH 22" (cardiac anomalies, abnormal facies, thymic hypoplasia or aplasia, cleft palate, and hypocalcemia). High-resolution chromosome analysis and FISH were performed on metaphases from 10 control subjects, 42 patients with features of CATCH 22, and 6 parents of children with CATCH 22. Patients were screened for conotruncal heart defect, palatal abnormality, and facial features. We correlated the phenotype, karyotype, and deletion of a D22S75 locus. Specimens from nine patients with one or more features of CATCH 22 had a single hybridization signal for D22S75, indicating a deletion of chromosome 22q11.2. Four patients had all the major features of the syndrome and a chromosomal deletion. Thirteen patients had two CATCH 22 features, five of whom had a deletion. None of the 25 patients with a single CATCH 22 feature had a deletion. One patient with a deletion detected by FISH also had a deletion noted on high-resolution banding. All six parents who had blood samples studied by FISH had normal hybridization patterns. FISH is a useful adjunct to chromosome analysis for assessing patients with features of CATCH 22. Detecting a chromosomal deletion by FISH provides a definitive diagnosis and helps to ensure appropriate medical management and genetic counseling.

1002-90 Deletions in Chromosome 22: A Common Cause of Conotruncal and Aortic Arch Defects

The acronym CATCH 22 (Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcemia from deletions in chromosome 22) has been coined to describe the occurrence of microdeletions at the 22q11 locus in 75–90% of patients with DiGeorge and Shprintzen syndromes. Because little data are available regarding the frequency of deletions in non-syndromic patients with congenital heart defects, we screened 61 patients with conotruncal cardiac defects and aortic arch abnormalities. Testing included FISH (fluorescent in situ hybridization) studies with the N25 (D22S75) digoxigenin-labeled DNA probe (Oncor, Gaithersburg, MD) and high resolution cytogenetic analysis. FISH revealed deletions in 8 of 20 patients with tetralogy of Fallot, 5 of 6 with absent pulmonary valve, 4 of 9 with pulmonary atresia/malalignment ventricular septal defect, 3 of 11 with truncus arteriosus, 4 of 8 with interrupted aortic arch, 1 of 2 with anomalous origin of the right pulmonary artery (hemitruncus), and 0 of 5 patients with double outlet right ventricle. Only 7 of the 25 patients with a deletion had a clinical diagnosis of DiGeorge or Shprintzen syndromes. FISH testing in 8 sets of parents demonstrated 3 individuals with deletions. These data show a high (41%) prevalence of CATCH 22 deletions in patients with congenital conotruncal or aortic arch defects. Early detection of patients with deletions facilitates genetic counseling and the identification of medical problems associated with CATCH 22 deletions.

Pulmonary atresia associated with maternal 22q11.2 deletion: possible parent of origin effect in the conotruncal anomaly face syndrome.

A blind study was designed to test the hypothesis that some persons with a relatively rare cardiac malformation, pulmonary atresia with ventriculoseptal defect (PA/VSD), have a recognisable phenotype. Fourteen patients with cyanotic congenital heart lesions were examined by dysmorphologists blinded to the type of cardiac malformation. Six children were judged to have a similar craniofacial appearance; all had PA/VSD. These children were not originally considered to fall within the classic phenotypes of the DiGeorge sequence or the velocardiofacial syndrome, both of which have been shown to be associated with deletions of 22q11. More recently, 22q11 deletions have been documented in the conotruncal anomaly face syndrome and apparently isolated conotruncal heart defects. A new acronym, CATCH 22 syndrome (Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcaemia) has been suggested to encompass this very broad phenotypic spectrum. A preliminary molecular study was conducted using the dinucleotide repeat D22S264 located on chromosome 22q11.2. All cases tested with the subtle but recognisable phenotype had deletions, all lacking the maternal contribution at this locus, suggesting there may be a parent of origin effect.